ABSTRACT: Core D: Clinical Research. The SPORE Clinical Research Core (CRC) has as its primary goal to be the direct translational link between research projects and clinical research emanating from these projects. The CRC is composed of the Clinical Trials Unit and the Molecular Epidemiology Resource (MER). The specific aims are to: 1) coordinate and perform SPORE clinical trial protocols; 2) manage SPORE observational epidemiology protocols and partner with the MER. The CRC provides a critical link between clinical research and the specific projects, cores, and developmental research. The CRC is led by the Director, Thomas M. Habermann, MD, at the Mayo Clinic Cancer Center and a Co-Director Brian Link, MD, at the Holden Comprehensive Cancer Center. A key function of the CRC is to coordinate the development of clinical trials, assist in patient accrual, manage protocol amendments, report adverse events to appropriate agencies, and provide comprehensive quality control on clinical trial data. For the MER, the CRC consents newly diagnosed lymphoma patients, abstracts and enters clinical and epidemiologic data, and systematically follows all MER patients through death. The CRC is linked to other SPORE cores providing SPORE investigators integrated and centralized access for projects. During the last funding cycle the CRC has been very active with 5 trials actively accruing patients and 4 new therapeutic trials initiated; overall 161 patients were accrued to these SPORE trials. Studies of novel agents such as the mTOR inhibitor everolimus were completed and published and moved to combinations with R- CHOP in the ALLIANCE National Clinical Trials Network group with promising results. Two trials using the immunostimulatory agent CpG were completed with CpG now incorporated into a new trial in Project 2. During the last funding cycle (through June, 2015), 2391 new patients were enrolled into the MER (cumulative total 7605 patients). Seminal, practice-changing publications in the areas of utility of PET/CT surveillance scans in diffuse large B-cell lymphoma (DLBCL), a new early endpoint - event-free survival (EFS24) for predicting long term DLBCL outcome, and transformation of follicular lymphoma (FL) in the rituximab era all originated from CRC research. The CRC also contributed to large genome-wide association studies in lymphoma, clinical observations in body mass index, complementary alternative medicine and trans fatty acid intake and risk were reported. 86 manuscripts have been published from activities involving this core in the last 4 years of this funding period. The CRC has worked with each of the Project Co-Leaders to plan the new clinical trials included in Projects 1-3 and continued use of the MER in Project 4. The CRC will also work with recipients of the Developmental Research Projects and Career Enhancement Program on any clinical or biomarker trials. The CRC has been vital to success of the SPORE and looks forward to continuing to serve SPORE investigators in the next grant.